The O'Brien Urology Research Center at the University of Michigan aims to address a broad range of basic, translational, and clinical concerns relevant to urological diseases. The center will build on a critical mass of urology investigators that comprise a well-established urology research program at the University of Michigan. Toward the O'Brien Center objective, five urology research projects have been assembled that reflect a wide range of investigation across various, different urological diseases. This broad spectrum of investigation is proposed to reflect the unique objective of the O'Brien Award mechanism, that being the advancement of urology research in general. The breadth of our proposed work thus spans from pediatric to adult urological diseases, and from basic science to clinical research. In Project 1, Dr. Jill Macoska will use cDNA microarray expertise, and a unique age-specific stromal and epithelial prostate model, to identify gene expression differences consequent to effects of aging on stromal-epithelial interaction. The findings will have implications for the pathophysiology of benign prostatic hyperplasia (BPH). In Project 2, Dr. John Park will use unique knockout models and cDNA microarrays to further characterize obstruction-induced COX-2 function in collecting duct cells, based on preliminary data implicating increased COX-2 expression in obstructive nephropathy. The findings may guide therapy development for obstructive nephropathy. In Project 3, Dr. Martin Sanda will use hybrid transgenic mouse models to characterize the role of FAS-mediated T cell death as a mediator of prostate-specific T cell tolerance. The findings will have implications for possible immune intervention in benign and malignant prostate diseases. In Project 4, Dr. John Wei and Dr. John Delancey will conduct clinical studies to identify intervention-specific, physiological/anatomic and racial determinants of urinary incontinence natural history and outcome. For this purpose they will use the Incontinence Symptom Index (ISI), a biometrically robust, validated, and broadly applicable instrument for measuring incontinence in multiple domains that they developed in preliminary studies. The findings should improve selection and evaluation of effective interventions for urinary incontinence. In Project 5, Dr. Mark Day will build on preliminary data implicating Rb and androgen receptor (AR) interaction in the regulation of prostate growth to characterize how Rb/E2F1 regulates AR trasncription and activity in vitro and in vivo. The findings have relevance to prostate growth and BPH. These 5 projects will be complemented by a Developmental Award Program that will further broaden the scope of this O'Brien Center to include new investigators in areas such as infertility and urological epidemiology, among others. Interaction between Projects will be facilitated by arl Administrative Core that will provide scientific oversight in the form of a multidisciplinary Center Advisory Board as well as biostatistical support in the form of biostatisticians with expertise in eDNA array analysis and in standard analyses for preclinical and clinical models. By embracing a broad range of urology investigation that spans from clinical to basic science, from pediatric to adult urology concerns, the University of Michigan O'Brien Center aims at advances centered on the broad yet common theme of urological research, as uniquely defined by the O'Brien Urology Centers funding mechanism.